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Research Volume 125 | 2017
Neonatal Cord Blood Oxylipins and Exposure to Particulate Matter in the Early-Life Environment: An ENVIRONAGE Birth Cohort Study
Dries S. Martens,1 Sandra Gouveia,2 Narjes Madhloum,1 Bram G. Janssen,1 Michelle Plusquin,1,3 Charlotte Vanpoucke,4 Wouter Lefebvre,5 Bertil Forsberg,6 Malin Nording,2 and Tim S. Nawrot1,7
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Background: As part of the lipidome, oxylipins are bioactive lipid compounds originating from oxidation of different fatty acids. Oxylipins could provide a new target in the developmental origins model or the ability of early life exposure to change biology.
Objectives: We studied the association between in utero PM2.5 (particulate matter with aerodynamic diameter < 2.5 μm) exposure and oxylipin profiles in newborns.
Methods: Thirty-seven oxylipins reflecting the cyclooxygenase (COX), lipoxygenase (5-LOX and 12/15-LOX), and cytochrome P450 (CYP) pathways were assayed in 197 cord blood plasma samples from the ENVIR ON AGE birth cohort. Principal component (PC) analysis and multiple regression models were used to estimate associations of in utero PM2.5 exposure with oxylipin pathways and individual metabolites.
Results: A principal component representing the 5-LOX pathway (6 metabolites) was significantly positively associated with PM2.5 exposure during the entire (multiple testing–adjusted q-value = 0.05) and second trimester of pregnancy (q = 0.05). A principal component representing the 12/15-LOX pathway (11 metabolites) was positively associated with PM2.5 exposure during the second trimester of pregnancy (q = 0.05). PM2.5 was not significantly associated with the COX pathway during any time period. There was a positive but nonsignificant association between second-trimester PM2.5 and the CYP pathway (q = 0.16).
Conclusion: In utero exposure to particulate matter, particularly during the second trimester, was associated with differences in the cord blood levels of metabolites derived from the lipoxygenase pathways. These differences may indicate an effect of air pollution during in utero life on the inflammatory state of the newborn at birth. Oxylipins may be important mediators between early life exposures and health outcomes later in life.
Citation: Martens DS, Gouveia S, Madhloum N, Janssen BG, Plusquin M, Vanpoucke C, Lefebvre W, Forsberg B, Nording M, Nawrot TS. 2017. Neonatal cord blood oxylipins and exposure to particulate matter in the early-life environment: an ENVIRONAGE birth cohort study. Environ Health Perspect 125:691–698; http://dx.doi.org/10.1289/EHP291
Address correspondence to T.S. Nawrot, Centre for Environmental Sciences, Hasselt University, Agoralaan gebouw D, 3590 Diepenbeek, Belgium. Telephone: 0032-11 26 83 82. E-mail: firstname.lastname@example.com
The Swedish Metabolomics Centre (http://www.swedishmetabolomicscentre.se) is acknowledged for outstanding assistance with the UPLC-ESI-MS/MS analysis.
This work was supported by grants from the European Research Council (ERC-2012-StG310898), ERA-NET ACCEPTED, Flemish Scientific Fund (FWO, G073315N/G0A7814N), and the Swedish Research Council Formas.
The authors declare they have no actual or potential competing financial interests.
Received: 8 December 2015
Revised: 1 October 2016
Accepted: 8 October 2016
Published: 4 November 2016
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Human exposure to particulate matter (PM) as a part of ambient air pollution has a substantial impact on human health outcomes such as cardiovascular morbidity and mortality and respiratory disease (Brunekreef and Holgate 2002; Nawrot et al. 2011). In 1990, Barker hypothesized that adult diseases are already programmed by the environment in fetal and infant life (Barker 1990). Indeed, recent findings suggest that indoor and outdoor exposure to environmental PM during in utero life is associated with adverse fetal outcomes including lower birth weight (Farmer et al. 2014; Glinianaia et al. 2004; Winckelmans et al. 2015). Underlying biological mechanisms involved in PM induced adverse health outcomes remain largely unknown, but indications of the involvement of inflammatory processes and oxidative stress are rising (Farmer et al. 2014; Proietti et al. 2013; Risom et al. 2005). PM-induced metabolic alterations might provide new insights into underlying biological pathways. Lipidomics elucidates complex structures and biological function of lipids (Shevchenko and Simons 2010), and might be important to understand the gene–environment–health paradigm. Unlike the genome, the lipidome (as part of the metabolome) is a very dynamic system that reflects the metabolic phenotype of the human body (Shevchenko and Simons 2010; Smilowitz et al. 2013). As part of the lipidome, oxylipins are bioactive lipid compounds originating from oxidation of different fatty acid (FA) precursors such as the ω-3 FAs (α-linolenic acid, docosahexaenoic acid, eicosapentaenoic acid) and ω-6 FAs (linoleic acid, arachidonic acid) (Zivkovic et al. 2012). Biologically active oxylipins are synthesized from these precursors primarily through the cyclooxygenase (COX), lipoxygenase (5-LOX and 12/15-LOX), and cytochrome P450 (CYP) enzymatic pathways. Oxylipin alterations have been studied in various disease contexts and may play important roles in acute and chronic inflammatory processes such as asthma, chronic bronchitis, chronic obstructive pulmonary disease, cystic fibrosis, and atherosclerosis (Conrad 1999; Eiserich et al. 2012; Lundström et al. 2011a; Tourdot et al. 2014). A growing body of knowledge in the field suggests that oxylipins may be used as biomarkers of metabolic health and disease (Zivkovic et al. 2011), and oxylipins may potentially be influenced by early life exposures. Both pro- and anti-inflammatory properties of oxylipins have been described, and environmental factors affecting these oxylipin levels remain a topic of interest (Caligiuri et al. 2014; Dennis and Norris 2015). There is limited information on the influence of air pollution on oxylipin pathways and metabolites, but recent experimental studies using mouse models of atherosclerosis suggest that exposure to ultrafine particles (UFP) (Li et al. 2013, 2015) and diesel exhaust (DE) (Yin et al. 2013) may increase levels of linoleic and arachidonic acid-derived oxylipins in different tissues and plasma. Oxylipin profiles in 18 nonasthmatic adults differed between bronchoalveolar lavage fluid (BALF) samples collected after exposure to subway air pollution versus ambient air (Lundström et al. 2011b). These findings indicate a potential role of oxylipins as relevant biomarkers in linking air pollution and adverse health outcomes.
The exposome encompasses the totality of environmental and external exposures, including exposure to combustion particles in the environment and subsequent physiological interaction with the genome, proteome and metabolome (Rappaport and Smith 2010; Wild 2012). The "pregnancy exposome" is important both as the starting point of the life-course exposome and because of the high vulnerability of the fetus to effects of environmental factors. Here, we studied associations of cord blood plasma oxylipin profiles with in utero exposure to air pollution (PM2.5; exposure with aerodynamic diameter < 2.5 μm) as a potentially important component of the pregnancy exposome. We measured 37 different oxylipins from the three main biosynthetic pathways (COX, LOX, and CYP) to study the potential influence of in utero PM2.5 exposure on these pathways and individual metabolites in the newborn.
Study Population and Data Collection
This study is part of the ongoing ENVIRONAGE (ENVIRonmental influence ON AGEing in early life) birth cohort and complies with the Declaration of Helsinki and was approved by the Ethics Committee of Hasselt University and East-Limburg Hospital in Genk, Belgium. For the present study, we included 222 mother–newborn pairs (only singletons) from the ENVIRONAGE birth cohort, recruited between Friday 1200 hours and Monday 0700 hours from February 2010 through April 2014 from the East-Limburg hospital in Genk. Twenty individuals were excluded because cord blood plasma samples showed hemolysis, 4 were excluded because of a lack of exposure data, and 1 was excluded because of missing information on maternal smoking, resulting in a total study population of 197 individuals. The catchment area of the hospital included the province Limburg in Flanders, Belgium, and combines both urban and suburban to rural areas with population densities between the municipalities ranging from 82 to 743 inhabitants/km2. The participation rate of eligible mothers in the birth cohort (mothers able to fill out a Dutch language questionnaire) was 61% and enrollment was spread over all seasons of the year. Participating mothers provided written informed consent when they arrived at the hospital for delivery. They completed study questionnaires in the postdelivery ward to provide detailed information on maternal age, pregestational body mass index (BMI), maternal education, occupation, smoking status, alcohol consumption, place of residence, use of medication, parity, and the newborn's ethnicity. Former smokers were defined as those who had quit smoking before pregnancy. Smokers were those who continued smoking during pregnancy. Based on the native country of the newborn's grandparents, we classified his/her ethnicity as European-Caucasian when two or more grandparents were European or non-European when at least three grandparents were of non-European origin. Maternal education was coded as "low" (no diploma or primary school), "middle" (high school), or "high" (college or university degree). The ENVIRONAGE birth cohort did not differ from all births in Flanders, Belgium, as to maternal age, education, gender, ethnicity, and birth weight (see Table S1) (Cox et al. 2013); but compared with all births in Flanders, our population was more likely to be primiparous (56% vs. 47%) and less likely to have had three or more previous births (10% vs. 18%). Cord blood samples were collected immediately after delivery, along with perinatal parameters such as birth date, gestational age, the newborn's gender, birth weight, and length, Apgar score, pH of arterial cord blood, and ultrasonographic data. Immediately after birth, all neonates were assessed for congenital anomalies and were considered healthy when the Apgar score after 5 min ranged between 7 and 10.
Exposure Assessment
Regional background levels of PM2.5 (μg/m3) were interpolated for each mother's residential address separately using a spatial temporal interpolation method (kriging) (Janssen et al. 2008). This method uses pollution data collected in the official fixed-site monitoring networks (n = 34) and land cover data obtained from satellite images (CORINE land cover data set; http://www.eea.europa.eu/publications/COR0-landcover) in combination with a dispersion model as described by Lefebvre et al. (2011, 2013). This model chain provides daily PM2.5 values using data both from the Belgian telemetric air quality network, point sources, and line sources which then are interpolated to a high-resolution receptor grid (25 × 25 m). The interpolation tool explained > 80% of the temporal and spatial variability (R2) in the Flemish region of Belgium (Maiheu et al. 2013). Total PM2.5 exposure for entire pregnancy duration was calculated as the mean PM2.5 concentration (μg/m3) of all pregnancy days. Date of conception was estimated based on ultrasonographic data (Janssen et al. 2012). Additionally, we calculated mean PM2.5 (μg/m3) concentrations during each trimester of pregnancy (1–13 weeks, 14–26 weeks, and 27 weeks until delivery). Address changes for 24 mothers (12%) who moved residence during pregnancy were taken into account when calculating exposures during the different time windows.
Sample Collection and Oxylipin Profiling by UPLC-ESI-MS/MS
Umbilical cord blood (mixture of arterial and venous blood) was collected directly after delivery in BD Vacutainer® plastic whole blood tubes with spray-coated K2EDTA (BD, Franklin Lakes, NJ, USA). Within 20 min after cord blood collection, samples were centrifuged at 3,200 rpm for 15 min to separate plasma from blood. Plasma was collected and stored in Eppendorf® tubes at –80°C until analysis. Cord blood plasma levels of total cholesterol and high-density lipoprotein (HDL) was measured using a Roche cobas c701 system (F. Hoffmann-La Roche AG, Basel, Switzerland). Oxylipin analysis was performed as previously described and validated (Gouveia-Figueira et al. 2015). Native, deuterated internal standards (IS) and the recovery standard CUDA (12-{[(cyclohexylamino) carbonyl]amino}-dodecanoic acid) were purchased from Cayman Chemical (Ann Arbor, MI, USA) or Larodan Fine Chemicals AB (Malmö, Sweden) (see "Chemical details for UPLC-MS/MS" in the Supplemental Material for details). All solvents were of HPLC grade or higher. A Milli-Q Gradient system (Millipore, Milford, MA, USA) was used to purify water used in UPLC mobile phase. In brief, oxylipins were extracted using a solid phase extraction (SPE) procedure on 60 mg Waters Oasis-HLB cartridges (Milford, MA, USA). Cartridges were washed and then preconditioned with MilliQ water buffer (5% methanol, 0.1% acetic acid). Next, 750 μL of cord plasma together with 10 μL antioxidant solution [0.2 mg/mL butylhydroxytoluene, EDTA in methanol/water (1:1)] and 10 μL of internal standard mixture (400 nM/standard, 12,13-DiHOME-d4, 9-HODE-d4, PGE2-d4, TXB2-d4) solution were applied on the cartridge. Cartridges were rinsed with 2 × 2 mL buffer and oxylipins were then eluted using 2 mL methanol and 2 mL ethyl acetate in tubes containing 6 μL 30% glycerol solution in methanol. Next, solvents were evaporated using a SpeedVAC system (Farmingdale, NY, USA). Residues were reconstituted in 100 μL methanol and the solution was transferred into LC-vials containing 10 μL recovery standard solution (5 ng/mL CUDA).
Profiling of oxylipins was performed by injecting 10 μL of the solution in the LC-vial on an Agilent 6490 triple quadrupole UPLC-MS/MS system equipped with the iFunnel Technology (Agilent Technologies, Santa Clara, CA, USA) operating in negative mode. An Acquity UPLC BEH C18 column (Waters) with in-line filter (2.1 × 150 mm, 130 Å, 1.7 μm particle size) was used at 40°C for chromatographic separation using a constant flow rate of 0.3 mL/min. The mobile phase consisted of a) 0.1% acetic acid in MilliQ water and b) acetonitrile:isopopanol (90:10) with the following gradient for acetonitrile:isopopanol (90:10): 0.0–3.5 min 10–35%, 3.5–5.5 min 40%, 5.5–7.0 min 42%, 7.0–9.0 min 50%, 9.0–15.0 min 65%, 15.0–17.0 min 75%, 17.0–18.5 min 85%, 18.5–19.5 min 95%, 19.5–21 min 10%, 21.0–25.0 min 10%. Peak identification and manual integration was performed using the MassHunter Workstation Software (Agilent Technologies). The stable isotope dilution method was used to quantify each metabolite using calibration curves of ratios of peak areas of native compounds by IS peak area (see Tables S2 and S3 for IS assignment to each native standard and calibration curves concentrations respectively). The recovery rates (%, mean ± SD, n) of the internal standards in the present study were as follows: TXB2-d4 (68 ± 18, n = 97), 12(13)-DiHOME-d4 (90 ± 13, n = 197), 9(S)-HODE-d4 (76 ± 19, n = 197), and PGE2-d4 (85 ± 23, n = 197). Samples with analyte peak areas below the limit of detection (LOD) were assigned a value of LOD/2 [LOD values were previously reported and are provided in Table S4 (Gouveia-Figueira et al. 2015)].
Statistical Analysis
For database management and statistical analysis, we used SAS 9.3 software (SAS Institute Inc., Cary, NC, USA). Metabolite concentrations were log10 transformed to approximate the normal distribution. For logarithmically transformed variables, we report central tendency and spread of data as geometric mean and interquartile range, respectively. Based on different pathways involved in oxylipin biosynthesis, metabolites were classified by the main biosynthetic pathways COX, CYP, 5-LOX, and 12/15-LOX (Figure 1; see also Table S4) (Zivkovic et al. 2012). We combined metabolites originating from the same pathway into different principal components using the PROC PINCOMP procedure in SAS 9.3. We derived unadjusted Pearson correlations for the first principal component of each pathway and PM2.5 during each time window. In our main analyses, we used separate multi-variable adjusted principal component regressions to estimate associations between in utero PM2.5 exposures and the oxylipin pathways, using the first principal components as the dependent variables in these models. The multi-variable–adjusted models were adjusted for gestational age, pregestational BMI, and maternal age as continuous variables; maternal smoking status (never, ex-smoker, current), maternal education (low, middle, high); newborn gender; cord blood total cholesterol and HDL concentrations (continuous); batch; and sample storage time. Due to correlations between different exposure windows (trimesters of pregnancy) of PM2.5, models of trimester-specific associations were additionally adjusted for PM2.5 exposure during the other trimesters. We applied the Benjamini–Hochberg false discovery rate (FDR) correction for multiple testing (represented by a q-value) based on the four different pathways and four different exposure windows tested (total number of tests = 16). Pathway models were classified as significant when q-values where ≤ 0.05. Individual metabolites from significantly associated pathways revealed in the main analysis by principal component regression were tested in a secondary analysis for PM2.5 dependency during the different significant exposure windows using multiple linear regression models. Estimates (beta-coefficients) of the principal component regression models and percent change in individual metabolite concentration (nM) are presented for each 5 μg/m3 increase of PM2.5. Q-Q plots of the residuals showed a normal distribution (data not shown).
Figure 1. Metabolic scheme of targeted oxylipins. Oxylipin synthesis via different biosynthetic pathways, COX, 5-LOX, 12/15-LOX, and CYP from their corresponding precursor fatty acids, arachidonic acid, eicosapentaenoic acid, dihomo-γ-linolenic acid, and linoleic acid (Zivkovic et al. 2012). All shown metabolites were targeted except for 5-HPETE (5-hydroperoxy-eicosatetraenoic acid), LTA4 (Leukotriene A4), and PGH2 (prostaglandin H2) and classified by biosynthetic pathway. Nondetectable targeted oxylipins (17-HDoDE, Resolvin D1, and Resolvin D2) are not shown on the scheme. A list of full metabolite names is provided in Table S4.
Sensitivity Analyses
We performed the following sensitivity analyses for pathways with significant associations with PM2.5 during at least one exposure time window: models additionally adjusted for third-trimester apparent temperature (based on tertiles of third-trimester apparent temperature to account for potential non-linearity); models additionally adjusted for trimester-specific average NO2 concentrations; models that included PM2.5 concentrations during only one trimester; models that excluded women with a cesarean (C-) section or one of the following pregnancy complications: diabetes, hypertension, hypo- and hyperthyroidism, and mothers with an infection during pregnancy (n = 18); models that were not adjusted for gestational age; and models stratified by newborn gender. In addition, for each significant pathway, we modeled principal components that were derived after excluding unstable metabolites (defined as metabolites that were significantly associated with storage time) and metabolites with > 40% of sample concentrations < LOD.
Characteristics of the Study Population and Exposure Levels
General characteristics of the study population consisting of 197 mother–newborn pairs are presented in Table 1. Data presented are complete for all variables other than cord blood pH (n = 177). Average maternal age was 29.1 years and ranged from 19 to 44 years. Mothers had an average (± SD) pregestational BMI of 23.8 ± 4.7 kg/m2. Most women (70%, n = 137) never smoke cigarettes, and 44 women (22%) stopped smoking before pregnancy, whereas 16 mothers (8%) continued smoking during pregnancy. About 85% (n = 168) of the newborns were Europeans of Caucasian ethnicity. Five minutes after delivery, > 90% of the newborns had an Apgar score of 9 or 10. The newborns, among them 89 girls (45.2%) and 108 boys (54.8%), had a mean gestational age of 39.3 weeks (range, 33–41 weeks) and comprised 111 (56%) primiparous and 66 (34%) secundiparous newborns. Birth weight averaged 3,453 ± 420 g, ranging from 2,135 to 4,445 g. Among the newborns, 10 (5.1%) were preterm births (gestational age < 37 weeks) and 3 (1.5%) had a low birth weight (< 2,500 g). Mean cord blood plasma total cholesterol and HDL levels were, respectively, 69 ± 18 mg/dL and 31 ± 11 mg/dL. Among the mothers, 11 (5.6%) were diagnosed with gestational diabetes, 3 (1.5%) had hypertension, 1 mother (0.5%) had hypothyroidism, and 3 (1.5%) had an infection during pregnancy. In total 7 mothers (3.6%) had a C-section. Of the 18 mothers who experienced a pregnancy complications, 2 had a C-section. Cord blood plasma oxylipins were analyzed in three batches within 3 consecutive days and the average storage time for cord blood plasma samples was 84.6 ranging from 7.3 to 218.7 weeks. Table 2 displays the daily outdoor PM2.5 exposure levels averaged for each of the three trimesters of pregnancy. Average PM2.5 concentrations for the first, second, and third trimester of pregnancy were 15.5 ± 5.4 μg/m3, 15.4 ± 5.1 μg/m3, and 16.1 ± 5.2 μg/m3 respectively. During entire pregnancy, PM2.5 exposure concentrations averaged 15.7 ± 2.6 μg/m3. First- and third-trimester PM2.5 concentrations were inversely correlated (r = –0.57, p < 0.0001), whereas first- and third-trimester PM2.5 concentrations did not correlate with second-trimester PM2.5 concentrations (r = 0.09, p = 0.22 and r = 0.08, p = 0.26, respectively).
Table 1. Characteristics of mother–newborn pairs (n = 197) selected from the ENVIRONAGE birth cohort between February 2010 and April 2014.
Table 2. Outdoor PM2.5 (μg/m3) exposure characteristics for the 197 mothers included in this study from the ENVIRONAGE birth cohort.
Oxylipin Levels in Newborns
We targeted 37 different individual oxylipins in cord blood plasma and detected 34 of them. Resolvin D1, Resolvin D2, and 17-HDoHE were not detected above the LOD in any of the samples, so we excluded these metabolites from further statistical analysis. Mean cord blood plasma oxylipin concentrations (nM) are shown in Table S4. For 21 metabolites all samples were detected above the LOD, and for another 10 metabolites ≥ 94% of the samples were detected above the LOD (see Table S4). LTB4 was detected in only 28% of the samples, 12-oxoETE was detected in only 56% of the samples, and 9-HETE was detected in 77% of the samples. Three metabolites (9,10,13-TriHOME, 9,12,13-TriHOME, and TXB2) showed a significant negative association with storage time and were classified as unstable (data not shown).
Cord Blood Oxylipin Pathways in Association with Maternal PM2.5 Exposure
A heat map illustrating the correlations between the individual metabolites in each of the four studied oxylipin pathways is provided in Figure S1. For each oxylipin biosynthetic pathway (COX, CYP, 5-LOX, 12/15-LOX; see Figure 1 and also Table S4 for assignment), principal components were derived as linear combinations of different metabolites involved in each pathway. The first principal components explained 42–55% of the variance for the four individual pathways, and factor loadings were ≥ 0.54 for 28 of the 34 individual metabolites (see Table S5). Characteristics of the first principal components used in the multi-variable–adjusted principal component regression models are shown in Table S5. Both before (Figure 2) and after adjustment for gestational age, pregestational BMI, maternal age, maternal smoking status, maternal education, newborn gender, cord blood total cholesterol and HDL levels, batch and storage time in multi-variable–adjusted models, the 5-LOX and 12/15-LOX oxylipin pathways were positively and significantly (q ≤ 0.05) associated with in utero exposure to PM2.5 during the second trimester of pregnancy (Figure 3). The 5-LOX pathway also was positively associated with PM2.5 exposure during the entire pregnancy (q = 0.05), whereas the association with the 12/15-LOX pathway was positive but not significant (q = 0.19). Positive but nonsignificant associations were also estimated for the principal component reflecting the CYP pathway and PM2.5 exposure during the second trimester (q = 0.16) and the entire pregnancy (q = 0.5) (Figure 3). The principal component reflecting the COX pathway was not significantly associated with PM2.5 exposure during any time period. Results of the sensitivity analyses for 5-LOX and exposure during the second trimester and entire pregnancy, and for 12/15-LOX and exposure during the second trimester, were generally consistent with the main analyses (Table 3).
Figure 2. Unadjusted Pearson correlation plots with 95% confidence intervals between oxylipin pathways and PM2.5 exposure during the second trimester: (A) correlation with the 5-LOX pathway and (B) correlation with the 12/15-LOX pathway. PC1, first principal component.
Figure 3. Association between oxylipin biosynthetic pathways and in utero PM2.5 exposure during different time windows. Estimates are presented for each 5-μg/m3 increase in PM2.5. Models were adjusted for gestational age, pregestational BMI, maternal age, maternal smoking status, maternal education, newborn gender, cord blood total cholesterol and HDL levels, batch, and sample storage time. Trimester-specific windows were additionally adjusted for the other PM2.5 exposure windows (trimesters). Q indicates the multiple testing adjusted p-values using the Benjamini–Hochberg procedure.
Table 3. Sensitivity analyses for the 5-LOX and 12/15-LOX pathways in association with in utero PM2.5 exposure.
Individual Cord Blood Oxylipins Associated with Maternal PM2.5 Exposure
Associations between all metabolites (independent of pathways) with exposure during all different pregnancy time windows are summarized in Figure S2 and Table S6. After identification of aforementioned significantly associated oxylipin pathways with in utero exposure to PM2.5 during the second trimester and entire pregnancy, we further examined individual metabolites of the 5-LOX and 12/15-LOX pathways in association with these significant exposure windows (Table 4). Positive associations of 3 profiled 5-LOX metabolites [5-HETE, p = 0.03; 5-oxoETE, p = 0.03; 9(S)-HODE, p = 0.06] were estimated in relation with in utero PM2.5 exposure during second trimester. Exposure during the entire pregnancy was positively associated with the following 5-LOX metabolites: 5-HETE, p = 0.05; 5-oxoETE, p = 0.006; 9,10,13-TriHOME, p = 0.08; and 9,12,13-TriHOME, p = 0.05. Eight of the 11 targeted individual linoleic (13-HODE, p = 0.05), arachidonic acid (8-HETE, p = 0.02; 11-HETE, p = 0.02; 12-HETE, p = 0.02; 12-oxoETE, p = 0.03 and 15-HETE, p = 0.006), eicosapentaenoic acid [12(S)-HEPE, p = 0.02], and dihomo-γ-linolenic [15(S)-HETrE, p = 0.04] derived metabolites from the 12/15-LOX pathway were positively associated with in utero exposure to PM2.5 during the second trimester of pregnancy.
Table 4. Estimated percent difference in individual metabolite concentration (nM) from the 5-LOX and 12/15-LOX pathways in association with in utero PM2.5 exposure.
The key finding of our paper is that in utero exposure to PM2.5 during pregnancy is associated with levels of free circulating oxylipins in cord blood plasma, particularly oxylipins from the lipoxygenase pathway (5-LOX and 12/15-LOX). Several individual cord blood oxylipins included in the 5-LOX and 12/15-LOX pathways were associated with in utero exposure to PM2.5 during the second trimester. To our knowledge, this is the first extensive report on targeting 37 oxylipins in cord blood simultaneously by LC/MS-MS quantification. These findings elucidate new early-life effects of air pollution on the metabolomic level, more specifically at the level of oxylipins.
To date, evidence concerning PM-induced alterations of circulating oxylipin metabolites is limited to experimental findings in mice. Apolipoprotein E–deficient mice exposed to diesel exhaust for 2 weeks showed increased concentrations of oxylipins (5-HETE, 12-HETE, 15-HETE, and 13-HODE) targeted from the 5-LOX and 12/15-LOX pathway compared with FA-exposed mice. Plasma levels of 12-HETE and 13-HODE were significantly elevated in exposed mice compared with the FA controls, and in liver and large intestine tissue only 5-HETE showed increased concentrations in the exposed mice. In BALF samples, both higher levels of 12-HETE and 15-HETE were measured in the DE-exposed mice compared with the FA controls, showing different elevated oxylipins in different tissues (Yin et al. 2013). In 2013 Li et al. (2013) reported that plasma levels of 9-HODE and 12-HETE were significantly higher in LDLR-null mice exposed to UFP compared with mice exposed to FA. Findings for plasma 13-HODE and 5-HETE were inconclusive, but mean concentrations were higher in mice exposed to UFP versus FA (p = 0.16 and 0.19 respectively). In a second study of UFP exposed LDLR-null mice by Li et al. (2015), significantly higher levels of 5-HETE, 12-HETE, 15-HETE, 9-HODE, 13-HODE, and PGD2 were reported in intestine and liver tissue of UFP-exposed mice compared with FA-exposed mice. In plasma, only 12-HETE, 15-HETE, and PGD2 levels were significantly higher when comparing UFP-exposed with FA-exposed mice. Reported higher plasma levels of 5-HETE, 9-HODE, and 13-HODE in UFP-exposed mice compared with FA-exposed mice were inconclusive (Li et al. 2015). These findings in animal studies are in line with our reported associations of in utero PM2.5 exposure with oxylipin profiles of the 5-LOX and 12/15-LOX pathway. Exposure during the second trimester was associated with cord blood plasma levels of 5-HETE, 12-HETE, 15-HETE, 9-HODE, and 13-HODE. However, the COX-derived PGD2 metabolite was not significantly associated with PM2.5 exposure during any time period in our study population (see Figure S2 and Table S6). Findings from the experimental studies, which used mouse models of atherosclerosis and high diesel exhaust and UFP exposures [e.g., 360 ± 25 μg/m3 of UFP in Li et al. (2015) compared with mean PM2.5 concentrations of 15.7 ± 2.6 μg/m3 in our study population], cannot be directly compared with the findings from our observational birth cohort study. Nonetheless, the experimental findings are generally consistent and support our results. Our findings, supported by these animal-based studies, suggests an important role of PM exposure in the alteration of the 5-LOX and 12/15-LOX pathways and derived oxylipins.
Our findings indicate possible early immunological alterations due to early-life exposure to particulate air pollution. Indeed, B-lymphocytes are able to produce the major 5-LOX metabolites 5-HETE and LTB4 in the presence of exogenous arachidonic acid and oxidative stress (Jakobsson et al. 1995). Grant et al. (2011) showed that the more biological active 5-oxoETE was produced in human B lymphocyte cell lines from its precursor 5-HETE after subjection to oxidative stress by H2O2. These findings suggest the ability of PM to induce oxidative stress by producing reactive oxygen species (ROS), which might stimulate the production of 5-HETE and 5-oxoETE in different types of leukocytes, reflecting a higher inflammatory state. However, the exact sources of the oxylipin metabolites measured in cord blood for our study are unknown.
Metabolites of the 12/15-LOX pathway have been indicated in pro- and anti-inflammatory responses (Uderhardt and Krönke 2012). Anti-inflammatory effects of 15-HETE and 13-HODE are related to their ability to modulate the activity of the peroxisome proliferator-activated receptor γ (PPARγ), implicated in adipocyte differentiation regulation, fatty acid storage, glucose metabolism, and anti-inflammatory processes (Martin 2010). In contrast to the involvement in anti-inflammatory properties, 15-HETE has been described in pro-inflammatory responses involved in air-way inflammatory diseases and asthma (Conrad 1999; Larsson et al. 2014; Lundström et al. 2011b; Sachs-Olsen et al. 2010). Our findings suggest that the second trimester of pregnancy is a very susceptible period for exposure in altering oxylipins. A potential explanation for this observation could be the fact that during pregnancy the syncytiothrophoblast layer, which forms the barrier between maternal and fetal blood, gets thinner with gestational age, and until week 10 of pregnancy the size of fetal capillaries increases leading to enhanced maternal fetal exchange of nutrients and particles (Proietti et al. 2013; Wick et al. 2010).
Strong points of our study are the high-resolution exposure estimates and integration of daily exposures to estimate pregnancy-specific exposure windows. The epidemiologic angle from the early-life perspective enhances the relevance of our findings for public health beyond that of studies in patients or older population segments that might be confounded by multiple comorbidities and polymedication. However, our present study must also be interpreted within the context of its limitations. Metabolomics is a top-down systems biology approach to understand the gene–environment–health paradigm. Cord blood is an important matrix to study metabolomic changes in the context of perinatal programming. However, we are able to study the associations only on changes in profiles at birth and not during pregnancy, which might be a limitation. Our sample size was relatively small, which might reduce the generalizability. Next, we analyzed oxylipin metabolites only in cord blood and not in maternal plasma during pregnancy, having only one snapshot at birth with no insight into the maternal link to the fetal oxylipin profiles. Keeping in mind the redundancy and bidirectionality in many metabolic pathways, studies such as ours cannot determine whether a metabolite is increased because of increased production, decreased degradation and/or uptake, or both. We also need to address the importance of maternal nutrition on the oxylipin state of the newborn, which may be an important factor influencing oxylipin levels that could not be taken into account in the present study. Essential fatty acids such as the ω-3 FA α-linolenic acid and ω-6 FA linoleic acid, which are precursors for oxylipin synthesis, have to be provided to the fetus by maternal nutrition (Herrera 2002). Because there exists a linear correlation between maternal intake of dietary fatty acids and maternal plasma and cord blood plasma concentrations of fatty acids, these might influence newborns' oxylipin levels (Donahue et al. 2011; Herrera 2002). However, we do not expect exposure to air pollution to be associated with omega-fatty acid consumption in our study population, so it is unlikely that these nutritional aspects have confounded our reported associations. However, we cannot completely rule out unmeasured factors including nutrition that correlate with air pollution or its variation over seasons. Although we have used a standardized fine-scale exposure model for the estimation of residential fine particulate matter, maternal daily activity patterns could not be taken into account which contribute to maternal exposure levels. Furthermore, PM2.5 might present an epiphenomena or a proxy for exposure to other air pollutants. However, the observation that only PM2.5 was statistically significant in two-pollutant models (including both nitrogen dioxide and PM2.5) highlights the independent role of particles. However, we did not address to what extent specific constituents of the particulate matter were responsible for the observed associations. Finally, epidemiologic studies demonstrate association, and the interpretation of the association with the metabolic marker rests on review and interpretation of the literature, which involves some degree of speculation. Nevertheless, our observational findings in mother–newborn pairs add to existing knowledge in the field of effects of air pollution exposure on oxylipin levels.
To our knowledge, our study is the first to report positive associations of metabolites from the 5-LOX and 12/15-LOX pathways in newborns with in utero exposure to PM2.5. These findings gain new insights in the pregnancy exposome and in the role of lipid mediators. Because metabolic profiles are more closely related to the phenotype compared with transcriptomic and proteomic profiles (Patti et al. 2012), these findings of PM-associated alterations of oxylipin profiles might have implications in later-life development of air pollution associated diseases. However, the consequences of alterations in early-life oxylipin profiles for later life diseases must be further elucidated in further prospective evaluations.
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Lundström SL, Levänen B, Nording M, Klepczynska-Nyström A, Sköld M, Haeggström JZ, et al. 2011b. Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure. PLoS One 6:e23864, doi: 10.1371/journal.pone.0023864.
Maiheu B, Veldeman N, Viaene P, De Ridder K, Lauwaet D, Smeets N, et al. 2013. Identifying the best available large-scale concentration maps for air quality in Belgium [in Dutch]. Mechelen, Belgium:Flemish Institute for Technological Research (VITO).
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Patti GJ, Yanes O, Siuzdak G. 2012. Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 13:263–269.
Proietti E, Röösli M, Frey U, Latzin P. 2013. Air pollution during pregnancy and neonatal outcome: a review. J Aerosol Med Pulm Drug Deliv 26:9–23.
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Uderhardt S, Krönke G. 2012. 12/15-lipoxygenase during the regulation of inflammation, immunity, and self-tolerance. J Mol Med (Berl) 90:1247–1256.
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Zivkovic AM, Yang J, Georgi K, Hegedus C, Nording ML, O'Sullivan A, et al. 2012. Serum oxylipin profiles in IgA nephropathy patients reflect kidney functional alterations. Metabolomics 8:1102–1113.
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Down Hooded Jacket
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If you know me well of enough, than you would know that I'm a nutcase with a addiction to angst and heartbreak. Mostly all my stories are sad or down right fucked up...and might leave you crying or really pissed off. The reason I am saying this because the story I have in my head is beyond the lines I have crossed with rage and fire. So I am warning you all, I don't know what or why this percise plot came to mind but I can't stop thinking about it until I have it written down on paper. If you haven't notice...I am a little fucked up in the head to write such pain filled stories that has little to no happiness.
So if you are up to it...I am happy to take this dark journey with you.
A Bella/Rosalie Story
Rated M
(I do not own shit but my fucked up imagination)
Summary~ Rosalie and Bella has grown up in the same foster care program, even as little girls...they knew they would be best friends for life. Violently ripped away from each other at a young age, one sold and taken as the other adopted. They meet again thirteen years later...how can a Mother and daughter save a woman who is on the brink of losing her humanity?
Hope you like it. :)
This will be told in Rosalie POV all throughout...until the last three chapters of the story.
"Rosalie help! Don't let them take me! Please Rosalie you promised!"
"Shit" I hissed as the cold wet pillow hit my warm cheek, look like I have been crying in my sleep again. Waiting for the pain to subside, I threw the covers away from my sweaty frame and sat up rubbing my hands down my face. It was a routine that I have mastered throughout the last ten to eleven years, waking up in tears barely breathing as my body was soaked in tears and sweat...sometimes urine if I didn't always wake up in time. Her screams were like clock work, soon as I closed my eyes...I was pulled back to the nightmares. It never missed a beat, like it was enjoying my fear of seeing them take her away from me. It would replay in my mind over and over, her screams getting louder and louder. Throwing a glance at the clock, I sighed heavily knowing that I wasn't going back to sleep anytime soon. Quickly running a warm bath, stripping myself from my clothes. The water was steaming, but it didn't faze me as I lowered myself in the scolding hot water.
Nothing seems to bring me pain anymore...I was numb to it
Lying my head back and closing my eyes, I relaxed my body and drifted off in my own world that I have created against her screams...against the bad memories.
Running through the small gated backyard, I suddenly tripped and skinned my knees. The pain was undeniable as I pulled my knees to my chest. I felt smalls hands on my shoulders, some how the hands made my pain disappear. Looking up through teary eyes, I saw a small girl with brown hair and brown eyes looking down at me.
"Are you okay?"
Her voice was so soft and soothing that I forgot about my bloody knees and stood up. Brushing my dirty hands on my now holey pants, she smiled and grabbed my hand.
"I haven't seen you here before, are you new?" She asked walking us inside the house, she knocked on a big brown door and a tall woman walked out.
"What is it?" The woman says angrily glaring at the brown haired girl who still tightly had a hold on my hand. The girl glared back with just as much anger, I was scared that she was going to get in trouble because of me.
"She fell and skinned her knees...she is bleeding" The woman cursed under her breath and walked back in her room. The brown haired girl just shrugged and smiled at me, seconds later the woman came back with a white box and tossed it to the girl and slammed the door hard. The girl shook her head and pulled us in the bathroom. She helped me up on the counter, we struggled for a minute until I was seated. She was so small, I towered over her.
I wonder how old she was?
"You didn't answer my question, did you arrived today?" She asked cleaning the blood and dirt from my knees.
"Umm...Yeah I think, My brother told me he will come back for me in three days...I want my mommy" She froze for a second but relaxed and continue to tend to my knees. I was confused as to why my brother would leave me with complete strangers but he pinky promised to come back. mommymommy
"What is this place?" I asked curious to why so many kids were running around, she put two band aids on my knees and smiled at me. It felt much better and I hugged her and said thanks. She showed me her room, her room was the only kid room that had one bed and one dresser. I really didn't know where my room was, the lady never showed me when I arrived here three hours ago. It's a good thing though, my brother Jasper was coming back so it didn't matter. She showed me her book collections and barbie dolls. We stayed in her room all day until night when suddenly a loud bang was heard. She flinched violently but smiled at me when I gave her a scared look as I watched the door knob slowly turned.
"Don't worry...it's just James the father of this foster care family" She says in a shaky voice but her smile never wavered. My first impression of James was that he was taller and bigger than my brother. He had the same blond hair as me but his eyes were this dark almost cruel blue color.
He was scary
"Bella time for dinner, bring Rosalie with you...don't take all day you know how angry I get if I have to wait to eat" She quickly stood up and nodded with her face down and eyes casted down at his shoes.
"Yes James" He gave her a smirk and touched her chin lifting her face to his, it was a brief kiss to the lips that I barely caught it, he walked out and she turned to me.
"Ready to meet the family?" her voice cracked but her smile never left her face, she reached out her hand to me.
"You never answered my question...What is this place?" I asked taking her hand, she walked us to the door and she grabbed the knob but stopped. She gave me a sad look that broke my heart but scared me non the less.
"You're name is Rosalie...James called you that? Well Rosalie you are in foster care...an orphanage for kids with no parents." Orphanage? I don't understand, that's a big word for a seven year old to know. I looked at her and shook my head.
"No...My mommy is with my Daddy on a trip, my brother told me and he said that when they come back he will come back to get me" She didn't say anything but opened the door and pulls us out and down the hall.
"Rosalie! Open the door, Rosalie can you hear me...It's Alice sweetie open the door please" I shivered jumping out of the now cold water, reaching for a towel on the rack I walked over to the door and opened it. My sister came bursting inside with red puffy eyes. She grabbed my towel and opened it, scanning my naked body with fear stricken eyes, she sighed in relief when she didn't find any newly lines of cuts that already covered most of my body. I looked at her and felt a little pinch of pain at how scared she looked, I hugged her to me as she blew a breath out.
"I promise you I would never do that again...don't you trust me?" She held on to me so tightly, Alice was my older sister. I had two older brothers name Edward and Emmett. They all were triplets, Esme and Carlisle were my adoptive parents and they all were my family. It took me a long time to be comfortable around them...especially Edward and Emmett. Alot of patience and love, I finally opened up and slowly let myself care for them.
"I do...it's just I get scared when you do that, I hate it when you lock yourself in the bathroom and we don't hear from you for hours" I rubbed her back, she was scared for me and I couldn't blame her. The last time she found me in my bathroom, I was under water bleeding from both of my wrists.
"You know it's the only way for me to have some type of peaceful sleep when I'm in water...She can't get to me there"
"I know, come on let's get you dressed and we can go to my room and I can run my hands through your hair until you fall alseep" I smiled grateful because I didn't want to go back to my bed. Quickly throwing my pj's on, we made it to her room. I crawled inside her big comfy covers and smiled, I always did love Alice's pillow top bed...it was like you were sleeping on clouds. She smiled and got under the covers with me, I didn't waste time in cuddling up to her as her fingers ran through my hair.
"You know you're getting too old for this Rosalie, I can't always be there for you when you get a nightmare. You're Twenty...turning twenty-one in a couple of months" She says softly
"Alice I can't function in this world if I don't have an anchor holding me here...And you are my anchor, you are my sister...so it's your duty to keep the bad dreams away" I let my words sink in, she wrapped her arms around me and sniff. I made her cry again! I'm always hurting somebody in this family, I was never good enough to be a Cullen anyway.
"Go to sleep Rosalie...I will be here when you wake up" I stuck my pinky out to her, she smiled and curled her pinky around mine and kissing them both.
"I love you"
"Bella I'm scared...I want my mommy" I whispered through the dark room, Bella had argued and whine for them to let me share a room with her after my little episode a couple of days ago. It's been a whole week and my brother broke his promise. It was a heated argument because, Bella never shared a room according to Jessica because James forbid it...her room was off limits. The mom finally broke and allowed me to share a room with Bella, James was furious but kept his anger at bay. So now here we are, I always slept with my unicorn nightlight. The dark always scared me, and now wasn't any different. I could hear her moving as I felt her body next to mine, she wrapped her arms around me and I snuggled into her chest. She cuddles just like my mother.
Oh how I miss her...I have been here for a week now, I was getting nervous that they forgot about me.
"Bella how old are you?"
"Nine" she says sleepy, she tighten her hold on me as I closed my eyes and felt my body relax. Then suddenly we both hear the door open, I felt Bella's grip on me tighten as She looked at me.
"Rosalie I want you do me a favor okay?" She asked as I saw tears start to weld in her eyes. I nodded and jumped when James voice came through the room.
"Let the little bitch sleep and get your ass over here now" his voice was much colder than normal. He never came in here at night...so why now? What was he going to do?
"Rosalie I will need you to close your eyes and think about a happy day with your family. But you have to keep your eyes close for me...Don't open your eyes until I tell you okay?" I quickly closed my eyes and nodded, I felt her lips on my forehead and then nothing. I wanted to open my eyes so badly but I promised her I wouldn't. So I did exactly what she asked and dreamed of a happy day with my family...
Hate it? Love it? Tell me what you think...


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House plants
Flowering house plants will flower year after year if given the proper conditions.
House plants can brighten and beautify almost any room and greengate can help you select the right plant for your home or offices specific conditions and offer you expert advice on care. There are two main classifications of houseplants - foliage plants, which include both standing and hanging plants, and flowering plants. Foliage plants are grown, obviously, for their leaf shape, colour, and often variegation. These plants may flower, but they are generally grown for their foliage, as their flowering is not consistent. Flowering houseplants will flower year after year if given the proper conditions.


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Sunday, 2 January 2011
I've got the blues
7 comments:
I've made that my aim too! I love getting comments so I'm gonna try and give them more!ReplyDelete
To be honest, I just chat a load of crap on Twitter, haha! xx
the colour of that dress is gooorgeous!ReplyDelete
ps; we WILL succeed in commenting on (each others) blogs this year :-)
That dress is so gorgeous!ReplyDelete
Christmas come down I hate it. The good thing about working in retail is that Christmas is over after Christmas day so I dont have that dreaded back to work feeling. Gorgeous dress fab colour on you. Hope your first day back at work is not too bad xoxoReplyDelete
I love Asos :):)! Cute dress!ReplyDelete
I saw your comment on Cupcake Couture's blog and I've got short hair too and spent ages looking for a way to get it up into a beehive-ish style and then I found this:ReplyDelete
I haven't tried it yet but I hope to soon, just thought maybe you'd like to check it out :) x
Thank you for all your lovely comments, they really make my day!ReplyDelete
@Little Mittens, thanks chick I shall check it out. I have some really short layers so if I can hide them I will try it out and maybe even post a photo or two xx


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Love and Candy
I love this swirly candy look!
But before I get to that, let me tell you how happy I am! I just spent the weekend with my dad, and he's planning to move to Asheville, along with my stepmom, my brother, my sister-in-law, and my niece. In one fell swoop, I will officially have a tribe!! Happiness is bubbling over!!
Anyway, back to the art, which I know is why you're here. It started out kind of bland, take a look:
When I took the tape off, I knew the letters needed more interest, so I took a chance and added some lollipop swirls. It turned out better than I expected.
It's ridiculously cute as a bag, whether big or small or wallet-sized:
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By Faith Teel
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Bring LOVE home!
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September 2017


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On-line Magazine 'Sensors & Transducers' (S&T e-Digest)
No. 3, March 2003
Table of Contents
The Number of IFSA Members has Exceeded Three Hundreds
March 3, 2002, Toronto, ON – International Frequency Sensor Association (IFSA) announces that number of IFSA members has exceed three hundreds. IFSA was created in 1999 as professional association with the aim to encourage the research and development in the area of smart sensors with frequency, time interval, duty-cycle and digital output, including multifunction, multifrequency transducers, the usage of new physical effects and principles. Having a successful record of joint research actions and of consulting services in the smart sensors field, the members of IFSA have considered the evolution of smart sensors technologies, MEMS and advanced signal processing methods and have come to realize the potentials for a wide scope of joint effort in the modern industry.
IFSA publishes the regular monthly IFSA Newsletter (ISSN 1726-6017) and Sensors & Transducers e-Digest (ISSN 1726-5479) that contributes to the adoption of new technologies, sensing principles, methods of measurements and design practice in the World.
IFSA President - Prof. Nikolay V. Kirianaki, has noted: 'Our members represent 55 countries today. 70 % of our members are from the industry, 30 % - from universities and academia. It is big corporations like ABB, Analog Device, Bell Technologies, Bosch, IMEC, Keller, Mazda, Melexis, Motorola, Sandia Labs and Yokogawa, government and military organizations as NASA (USA) and US Navy, different SMEs and individual members. IFSA members have free access to a wide variety of sensors related information: reports on different strategic and current IFSA activities, invitations to sensors related events, papers and articles'. Members present their related products, services, technologies and expertise to the worldwide public in order to be found by potential customers and/or cooperation partners. They have also a discount for all Sensors Web Portal services.
'The main objective of IFSA in 2003 is consolidating the participation of all major smart sensors manufacturers, R&D centres and Universities, is to progressively establish partnership in this promised high-technological area' – added Prof. Kirianaki.
Please click <here> to download the press release in PDF format.
Dr. Sergey Y. Yurish
|Universal Induction Magnetic Field Sensor/Transducer of High Sensitivity
Single (fig. 1) and triaxial (vector) wide-band induction sensors/transducers have been designed for measuring magnetic field strength which are highly-sensitive. High quality design and circuit adopting ability to varying conditions is guaranteed. Their average magnetic field sensitivity is 1pico -1femtoT/Hz in the frequency range 1Hz -1MHz, their overall dimensions 210x210x210 mm, weight 0.85 kg and takeoff power 0.2 W. They can withstand environmental exposures to: temperature from -50 to 70 Celsius and mechanical shocks up to 50g. For more information please click <here> to download the press release in PDF format.
Dr., Rostyslav Sklyar,
Space Sensing Instruments,
Verchratskogo st. 15/1, 79010, Lviv, Ukraine
Tel/Fax: +380 (322) 762432 / 769613
E-mail: firstname.lastname@example.com
|Figure 1.
|Figure 2.
Time-to-Digital Converters Based on the
A set of time-to-digital converter (TDC) modules in different standards (VME, NIM, PCI) based on a proprietary ASIC (AMS110) has been built. These modules, which have four channels and a common input, are particularly suitable for the readout of multi-wire proportional wire chambers (linear and area detectors) and time of flight experiments on synchrotron radiation and neutron sources.
(CORDIS focus, Issue No.40, Feb.2003, p.30)
Christian Herve,
European Synchrotron Radiation Facility (ESRF)
F-38043 Grenoble
Tel: +33-476-882047
Fax: +33-476-882020
E-mail: email@example.com
Scalers and Data Acquisition
A modular data acquisition system, including software, using individual scalers for parallel readout of individual detector elements, has been built and tested. The system can be used with e.g. multi-wire detectors and silicon pad or microstrip detectors.
(CORDIS focus, Issue No.40, Feb.2003, p.31)
Christian Boulin,
European Molecular Biology Laboratory,
Meyerhoffstr. 1
D-69127 Heielberg
Tel: +49-6221-387350
Fax: +49-6221-387242
E-mail: firstname.lastname@example.com
Industrial Grade Dynamic Pressure Sensors
The series is available with either a 2-pin military connector or an integral, molded, submersible cable assembly. The hermetically sealed stainless steel construction protects against contamination and permits use in harsh industrial applications. The devices offer the unique ability to detect very small pressure fluctuations in the presence of high static background pressures. Typical applications include detection of dynamic pulsations, surges, water hammer, cavitations, and spikes in liquid delivery systems, paper slurry systems, pumps, and compressors.
Andrea Mohn
Marketing Assistant
PCB Piezotronics, Inc.
3425 Walden Avenue
Depew, NY 14043-2495
E-Mail: email@example.com
|Family of 4 to 20 mA Vibration Monitoring Equipment
When the vibration of bearings, gears, and running speed is monitored, excessive wear and potential failure can be identified, and catastrophic failure or unscheduled downtime may be prevented. Overall vibration levels represented by 4 to 20 mA signals are monitored by IMI devices, with threshold points providing the judgment for alarm, control, or shutdown. These signals may be interfaced with existing PLC, DCS, alarm, control, and SCADA equipment.
Signal conditioners convert dynamic ICP® sensor signals into 4 to 20 mA analog signals representing RMS or peak values; loop-powered 4 to 20 mA sensors are available with peak velocity, RMS velocity, or RMS acceleration output signals. Indicator and alarm modules feature adjustable time delays to eliminate false alarm trips due to momentary vibration upsets.
Eric G. Yax
Sales Manager
IMI Sensors Division
3425 Walden Avenue
Depew, NY 14043-2495
E-Mail: email@example.com
|Measure 32 Accelerometers Using ONE Cable with DSIT Technology
Measure up to 64 channels per chassis with remote DSITs performing 24-bit analog-to-digital conversion near ICP® accelerometers and transmitting their signals back digitally via low cost ribbon cable. Link chasses with synchronous sampling to build high channel count systems at low cost per channel without sacrificing performance. System features include 110 dB dynamic range, TEDS compatibility, Ethernet communication and fan-less operation.
John Rehard
Division Manager,
Larson Davis, Inc.
1681 West 820 North
Provo, UT 84601
E-Mail: email@example.com
Smart Sensors Networks Need Smart Net Tools
The smart sensor networks systems are designed to provide an attractive alternative to typical measurement systems using large numbers of sensors. One of more significant benefits of these systems is a reduction in the number of interconnecting cables. Other benefits include a standard transducer-to-network interface to accommodate any type of sensor or actuator, a communication protocol that provides for high speed synchronized data collection and flexibility.
Very often, data acquisition devices that collect data from smart sensors in sensors network contain an Ethernet interface. The rising popularity of Ethernet and Internet is reflected by rising effort of manufacturers to include Ethernet TCP/IP interface into smart sensors. Today, Ethernet is most promising networking technology for use in automation. In order to monitoring such kind of sensor network by proper way it is necessary to use special network tools. Fortunately, a lot of them are the same like is used in Local Area Network (LAN). Let me consider some of Fluke Networks NetTools for ensuring reliable data communications.
4300 Digital Cable Analyzer - high-Performance, cat 6 twisted-pair and fiber cabling testing plus comprehensive data management. The DSP-4300, the newest member of Fluke Networks family of digital cable analyzers, is the most comprehensive test solution. The new DSP-4300 offers more testing flexibility with expanded on-board memory. Save valuable time and download the cable IDs for the job in the office. The DSP-4300 includes superior digital test technology, delivering consistent, repeatable accuracy. Equipped with on-board memory, a removable memory card, and a PC card reader, the DSP-4300 enables instant data hand-off so the tester stays on the job. Test report generation is quick and easy using the free CableManager software. Depending on your needs, choose from several reporting formats — from basic text summaries to professional color graphical reports.
NetTool Tester - A powerful, easy-to-use test tool that every frontline network technician will use everyday. Conclusively identifies a jack as Ethernet, phone, token ring or inactive; Helps quickly verify and troubleshoot connectivity; Resolves complex network configuration issues such as IP address, default gateway; Checks link pulse for speed, polarity, duplex, level information and receive pair; Simultaneously monitors network health (frames sent, utilization, broadcasts, errors, collisions) for full-duplex connections; Shows protocol mismatches between the PC and the network, and identifies unwanted protocols that waste valuable bandwidth.
620 LAN CableMeter - Features: Tests all LAN cable types: UTP, STP, FTP, coax; Reduce time and cost — test each connection "As You Go," without the need for a remote unit termination or a connector at the other end of the cable; Verifies end-to-end connectivity per selected wiring standard; Detects wiring problems: open, short, miswires (transposed, reversed, split pair); Locates wiring/connection errors (distance to the open or short) and measures cable length; Verifies cable routing and cabling labels (with "cable identifier").
For more details about Fluke Networks NetTools please click <here>.
Environmentally-Friendly Melt Pressure Transducers
The Series 2000 range of Melt Pressure Transducers is now available from Magna Projects & Instruments. The patented innovative design allows accurate pressure readings to be made in laboratory rheometers, pilot plant, and processes such as plastics, food and pharmaceutical extrusion and mixing, without the need for the traditional transmission-liquid filling of mercury or sodium-potassium, which can lead to product contamination if these transducers break. As well as being suitable for general use, the Series 2000 is an attractive choice for sensitive applications such as pharmaceuticals, film, medical product production, biological materials testing, food manufacture and for energetic materials. They may be operated via an intrinsically safe barrier for hazardous-area use. The wetted parts are of stainless steel, with a Di-Hard ® corrosion and abrasion-resistant tip on the standard transducers. For more demanding applications, coatings of Titanium Nitride and Hastelloy are available. Additionally, an integral Type J or Type K thermocouple can be fitted.
For more details please click <here> to download the press release in PDF format.
Barbara Carter
Magna Projects & Instruments Limited,
Willow House, Braemar Close, Mountsorrel UK-LE12
Tel: +44-(0)116-210-6577
Fax: +44-(0)116-230-3606
E-mail: email@example.com
LabVIEW for Data Acquisition (book and CD-ROM edition)
by Bruce Mihura
An introduction to the LabVIEW graphical programming language for monitoring and controlling physical phenomena with a computer via electrical signals. These electrical signals are usually attached to scientific or industrial equipment by means of transducers that convert physical values like pressure, temperature, position, and flow rate. Mihura, who worked as a LabVIEW developer for National Instruments, addresses simulation techniques, debugging, real-time issues, and networked and distributed systems. The CD-ROM contains an evaluation version of LabVIEW 6i for Windows. Book News, Inc.®, Portland, OR.
For more information about LabVIEW books, CD and Magazine please click <here>.
Title: LabVIEW for Data Acquisition
(book and CD-ROM edition)
Author: Bruce Mihura
Publisher: Prentice Hall PTR
Binding: Paperback, 316 pages
Price: $US 68.00
1999 - 2004 Copyright ©, International Frequency Sensor Association (IFSA). All Rights Reserved.
Home - News - Archives - Tools - Standardization - Patents - Marketplace - Projects - Wish List - Subscribe - Search - e-Shop - Membership
Members Area -Sensors Portal -Training Courses - S&T Digest - For advertisers - Bookstore - Forums and Poll


text:
Board of Directors
If you would like to review the HSCC's by-laws, please contact any board member.
If you have a question or concern regarding the group, please contact the Executive Director at 434-821-3034. Board meetings are closed to the public but any questions or concerns that the Executive Director can not answer will be brought to the Board on a two week notice.
- Matt Smith, Chairperson, Executive Director
- Kathy Bryant, Secretary
- Amanda Williams, Treasurer
- Laura Critzer
- Laura Linn
- Jessica Gillum
- Currently open: a non-voting member representing Campbell County government


text:
Owen fell off his bed Friday night and broke his elbow. After a trip to urgent care, an x-ray, a temporary cast, a drive to the ER with me cradling him in my lap in the backseat, a consult from an orthopedic surgeon, a blown IV line, a second temporary cast, and me holding my precious baby boy at 1:00 in the morning under the harsh bright lights of an ER exam room while he sobbed that he just wanted to go home - a decision was made to admit him and operate in the morning to insert pins to put his elbow back together.
I think he might be the bravest boy in the entire world.
I was up every 1/2 hour with him in his room that night, moving him from hospital bed to chair and back, just trying to find some place where he could get comfortable enough to sleep. I gave up on sleep for myself at 6 a.m. My cell phone had long since died, I had nothing with me but my empty purse and the clothes on my back, I didn't dare turn on the tv or leave him for a moment. So I just stared at my baby for the next few hours until my mom came to sit with me.
Did I mention Scott was out of town at his grandma's funeral?
I ran on pure adrenaline the next morning. I held it together until they wheeled him away from me to the OR. The anesthesiologist had given him a sedative so he was pretty loopy when he left my sight which I hope made it easier for him. I lost it. Thank God for my mom, she got me through the next hour while he was in surgery.
They put 3 pins in his elbow during the surgery, and then did a split cast on his arm to allow for swelling. Scott made it to the hospital a couple hours after the surgery, after driving 8 hours in the snow and wind after just driving 8 hours the day before, missing his grandma's funeral to be with his son. What a choice.
They let us leave at 6:00 that night. You could see the relief in Owen's face when he realized he was finally going to go home and no one was going to poke or stick him with anything anymore.
He and I slept in my bed and didn't get up this morning until 10 a.m. We were up for a couple hours, then I started feeling terrible. Ashley took my temperature just to be cute, and I realized I had a 102 degree fever.
I'm feeling better now. The fever broke after a few hours and some more sleep, so I'm not sure if I picked something up at the hospital, or if my body was just trying to deal with the lack of sleep and adrenaline and stress. I also can barely walk. I think I pulled various muscles carrying and lifting and moving Owen, so I'm kind of a wreck right now.
He is doing so much better. His pain is way better, and we are just doing motrin now for pain control. He's cuddled up in bed with me right now snoring holding the stuffed giraffe I bought him in the gift shop while trying to stay sane during his surgery. We go back to the orthopedist in a week to do the full cast once his swelling has gone down. Then he'll have the cast on for 4-6 weeks, and then they'll take out the pins. I find it so relieving that the pins are temporary. The thought of my perfect little baby boy having permanent metal in his body totally upset me, so I felt so much better when I found out they are temporary.
Ugh. There is just nothing worse than seeing your baby in pain. Nothing.


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Date posted:2018-07-19 | Writer: Aksorn Thepprasit School, Pattaya, Chonburi | Email: email@example.com
An English Conversation/ Phonics Teacher is required to teach mainstream Primary 1 to 6 students in Aksorn Thepprasit School, Pattaya, Chonburi. The candidate must be enthusiastic, energetic and available to start immediately. Newly qualified TEFL teachers are welcome to apply. Conditions: - Salary: minimum salary of 37,000 baht. Some room for negotiation for candidates with qualifications in Education and teaching experience. - Full time positions - up to 21 hours teaching time per week. - Working hours: Monday to Friday 7:30 - 16:00 - BUPA Health Insurance (Ruby Classic) after a 3 month probationary period. - Paid annual leave - Work Permit provided by school. - Annual salary increment Essential: - A native level English speaker (Canada, the U.S., the U.K., Australia, New Ze... Read more
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Apply now to work in a well set up school where you can really use your TEFL skills to make a difference in your students' lives. Shane English School Thailand has schools across Thailand, but are currently looking for full-time EFL teachers to work in Bangkok and Chonburi. We are looking for qualified, fun, energetic and hard-working individuals seeking a fresh challenge to join our team. Shane English School is a well-established and highly respected chain of EFL (English as a Foreign Language) schools. We place great emphasis on providing a high quality, excellent value, and caring service to our students. Shane is a language school catering mainly to children and teenagers, you may also have adult and kindergarten classes. A lot of the teaching hours will be after school and at th... Read more
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Saparachenee School at Trang province in the South of Thailand is looking for 3 energetic and dynamic EFL teachers for the next school semester - starting immediately. Flexibility and motivation are of greater value than extensive experience. The applicant should be able to encourage and inspire students to love learning and excel in the subject area of English. Requirements: - Native level English speakers from UK, US, Australia, NZ, Canada and South Africa - TEFL/CELTA/TESOL certificate - University degree What can we offer you? - Salary packages 30,000 - 33,000 baht/ month depending on your qualifications - Assistance in finding and securing accommodation - Non-B Visa (working Visa) assistance - English speaking Thai consultants offering 24/7 assistance - Contracts with the o... Read more
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Teachers for Thailand is a teaching agency that specializes in uniting professional educators with qualified teaching positions in Thailand. Essentially, our job is to find TEFL work for you through a job that will fit both your personality and skills. Our company has more than 25 years of experience in education, management, and recruitment, allowing us to give you the best service possible. Teaching in Thailand is truly a unique experience, allowing you to discover its beauty far beyond what is possible through just tourism. We're not just enthusiastic about teaching, we love to teach and we want to help you get the most out of your experience. We have jobs in big cities to mid size towns, jobs near the beach and near the mountain. Bangkok, Nonthaburi, Samutprakarn, Chonbu... Read more
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We are Road Experience. We chose this name because we believe people discover more about themselves and the world around them when on the road. Our mission is to recruit qualified EFL teachers to teach English at Thai schools and to assist our teachers and schools every step of the way. We are one of the biggest agencies, with over +200 schools in our network from every age range, and region in the country. Teaching in Thailand is a wonderful opportunity to gain real work experience abroad while also earning enough income to travel within the country or to our beautiful neighboring countries. We have a number of positions with immediate starts as listed below: POSITION: English Teacher needed in private language centre in Chiangmai Positions Available:  ... Read more
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Chalermprakiatsomdetprasrinakarin School aka Srinagarindra, the Princess Mother School, Phuket is looking for an additional native English speaking EFL teacher to join our team and teach M1 to M6 (grades 7 to 12 students). The successful candidate will teach up to 18 hours per week, for a salary of 35,000 baht per month, and the school will provide all documentation for your work visa and work permit. The position is for an immediate start date, and the contract is for 1 year. TO APPLY: To be considered for an interview, email the following documents to the address given on the job heading: 1. CV/Resume 2) Passport ID page. 3) Bachelor's Degree (Preferably a Bachelor's Degree in Education). 4) TEFL, TESOL or CELTA Certification. 4) Police clearance document. ... Read more
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Shane English School is a well-established and highly respected chain of EFL (English as a Foreign Language) schools. Apply now to work in a well set up school where you can really make a difference in your students' lives. We have schools across Thailand and have regular opportunities for TEFL qualified teachers. We place great emphasis on providing a high quality, excellent value, and caring service to our students. Shane is a language school catering mainly to children and teenagers, although you may also have adult and kindergarten classes. A lot of the teaching hours will be after school and at the weekend. We are looking for qualified and hard-working individuals seeking a fresh challenge to join our team. We are a professional school: We have already prepared tests, course gui... Read more
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Date posted:2017-11-23 | Writer: Walailak University Language Institute | Email: firstname.lastname@example.com
Walailak University Language Institute in Nakhon Si Thammarat has vacancies for TEFL qualified teachers who are available to start work soon. Benefits include a salary of 40,000 Thai baht / month plus housing allowance, medical care and accidental insurance. Qualifications: 3.1 A native speaker applicant from the United States of America/United Kingdom/Australia/New Zealand/Canada OR a non-native speaker (non - Thai) applicant holding a bachelor's in English, Education, Teaching English as a Foreign Language, Linguistics, English Literature, or related fields. 3.2 Candidates with experience in Teaching English, including a TEFL qualification will be preferred. Teaching requirement: 1. Teaching English to Speakers of Other Languages (TESOL), designing and conducting other ... Read more
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Date posted:2017-10-04 | Writer: Mathus Language School | Email: firstname.lastname@example.com
Are you a person who loves working with kids? Does the idea that you can have a positive and lasting impact on a child's life excite you? Do you enjoy working with others to collaboratively come up with solutions to difficult problems? Mathus Language Academy is looking for EFL teachers to start ASAP for a one-year contract. We are the most well-known language school in Suratthani, with an excellent reputation which we work hard to maintain. We Offer: • Starting salary of 33,000 THB. Salary is negotiable based on experience and qualifications. • 15,000 THB end-of-contract bonus. • Accident insurance - from a private provider (AXA insurance plan 1) and access to social insurance. • Work permits and visas - no funny business or visa runs here. We're legit... Read more
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The Language School invites you to join our dream of educating and providing a better future for the children of Suratthani. This is a great opportunity for someone with TEFL skills to enjoy Thai culture and give back to the community. The position is teaching 25 classes a week of 16-30 students in a primary school and private language school Monday to Friday or Saturday to Wednesday. Plan & teach lessons using the lesson plan guidelines and materials provided. Complete speaking and written assessments with the children using the test material provided. DETAILS: • November to March contracts available (renewal decisions in January) • Probation month 300-350B per contact hour • 350 -400B per contact hour • Unpaid Induction Training / orientation • Paid... Read more
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Stoney Croft Bungalow Self Catering Accommodation
Just a short drive from the Wanted Inn we have our self catering bungalow located in the popular village of Castleton. This beautiful building is located close to the village centre and offers self catering accommodation for 10 people.
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text:
Wow, it's been a while since I've written on here, but I'm rather upset right now. Apparently Adbrite and Black Label Ads (same company owned both, one was adult ads the other was not) shut down in February 2013.
I just went to log in today because I could have sworn I was at payout in January 2013 but I never received a check. Well, surprise surprise, there is no site anymore. It's just a 404 error page.
I do a bit of looking about the web and low and behold, they announced the shut down and sent e-mails, but only some people got the e-mails. Others were as baffled as I about the sudden disappearance.
So now it's off to find another adult ad provider. Of course, I've now been sitting on a couple sites with no ads for a couple months (and never got paid my final payout, on top of that, and have no proof I earned it since the entire site is gone now).
Lesson learned. Log in bi-monthly, minimum, and take screenshots of your dashboard so you can file proof with the BBB if another ad company ever goes under.


text:
Pink has been in a relationship with Todd Morse.
Pink has had encounters with Tommy Lee (2003), Kristanna Loken (2003) and Joey Fatone (2000).
Pink is rumoured to have hooked up with Anthony 'Treach' Criss.
Pink is a 38 year old American Singer. Born Alecia Beth Moore on 8th September, 1979 in Doylestown, Pennsylvania, USA, she is famous for 'Can't Take Me Home' Single. Her zodiac sign is Virgo.
Pink is a member of the following lists: American contemporary R&B singers, 21st-century women musicians and 20th-century women musicians.
Help us build our profile of Pink!
to add information, pictures and relationships, join in discussions and get credit for your contributions.
Alecia Beth Moore (born September 8, 1979), known professionally as Pink (often stylized as ), is an American singer, songwriter, dancer and actress. She was signed to her first record label with original R&B girl group, Choice, in 1995. The label, LaFace Records, saw great potential in Pink, offering her a solo deal. Choice disbanded in 1998. Pink rose to prominence as an artist with her debut solo album Can't Take Me Home (2000). It was certified double-platinum in the United States and spawned two US Billboard Hot 100 top-ten songs: "There You Go" and "Most Girls". She gained further recognition with the Moulin Rouge! soundtrack, "Lady Marmalade", which gave Pink her first Grammy Award, as well as her first number-one single in the US. Pink took more artistic control and pursued a pop rock direction for her second album, Missundaztood (2001). It sold more than 12 million copies worldwide and yielded three US top-ten singles, "Get the Party Started", "Don't Let Me Get Me", and "Just Like a Pill".
Pink and Tommy Lee had an encounter in Nov 2003.
Pink and Kristanna Loken had an encounter in 2003.
Carey Hart and Pink have been married for 12 years. They were dating for 3 years after getting together in Jan 2001. After 6 months of engagement they married on 7th Jan 2006.
Joey Fatone and Pink had an encounter in 2000.
Anthony 'Treach' Criss is rumored to have hooked up with Pink.
Todd Morse is rumored to have hooked up with Pink.
celebrities like #tracikochendorfer #pink #bradleycooper show how escatic they are about #philadephiaeagles going to the super bowl as fans... go to social media https://twitter.com/Pink/status/955265910578733057
Soooo Cute ... better keep good records and photos ... cause they grow sooo darn fast ... off to college in nooo time.
I am a great fan of Pink, I especially loved her first CD.
Hello. Really a huge fan of Pink. Much success to her and her endeavors.
She isn't Jewish..
Father is Catholic and mother is Jewish; shedidn't get along well with her mom. She acknowledged only her dad made her both personally and professionally
Help keep Pink profile up to date.
Connect any celebrity with Pink to see how closely they are linked... romantically!